In normal cells, IRE1 activity is impaired under sustained ERS, which leads to PERK-mediated apoptosis (Lin et al., 2007); however, in melanoma cells, IRE1 activity is maintained through the MEK/ERK pathway, which counteracts the PERK-mediated apoptosis (Tay et al., 2014). Here, EIF2AK3 is linked to melanoma.